title: Disease-associated amyloid and misfolded protein aggregates activate the inflammasome.
abstract: The pathogenesis of type 2 diabetes, Alzheimer's disease and amyotrophic lateral sclerosis continues to be debated. Recently, the inflammasome protein complex has been shown to be a key regulator of IL-1β, a cytokine implicated in each of these diseases. In all three cases, it is now apparent that unique protein aggregates caused by inappropriate oligomerization or misfolding are sensed by the inflammasome, providing a unifying mechanism for this IL-1β production. What evolved as an innate defense against infection-related particles, therefore, now seems to be a driving force for inflammation in these diseases. This review discusses the basic research behind these findings and the potential for new therapeutic interventions this affords.
authors.affiliation: Immunology Research Centre, Inflammation Research Group, School of Biochemistry and Immunology, Trinity College Dublin, Ireland. smasters@tcd.ie
authors.forename: Seth L
authors.initials: SL
authors.lastname: Masters
authors.forename: Luke A J
authors.initials: LA
authors.lastname: O'Neill
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D058228:Islet Amyloid Polypeptide / Q000378:metabolism; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D058847:Inflammasomes; D058228:Islet Amyloid Polypeptide